The proposed research seeks to combine aspects of well established investigations in the behavioral pharmacology of cocaine in humans, with PET scanning methods. The aim is to quantify both regional cerebral glucose metabolism and dopamine D2 receptors in the human brain in response to single dose and repeatedly administered cocaine. The first series of studies will establish the location and magnitude of the perturbations in these brain changes, using a Magnetic Resonance Imaging overlay technique in the case of glucose metabolic changes for additional accuracy in site localization. The size of changes relative to administered dose of cocaine will also be assessed. Using glucose metabolic measures, we will explore whether a diminution in activity accompanies the development of pharmacological tolerance to cocaine's effects. A second series of studies will examine the cerebral basis of the action of the tricyclic desipramine and the dopamine D2 antagonist haloperidol in interfering with self-report of cocaine's effects. Parallel experiments will explore the action of these agents in modifying or blocking cocaine's effect on the dopamine system and regional cerebral glucose metabolism as determined in the first series of studies. Changes in brain chemistry, especially in the dopaminergic system have long been held to underlie many of cocaine's behavioral effects. These experiments will test those hypotheses, and more importantly will examine the interaction of putative treatments for cocaine abuse with these chemical changes.